Typical neurodegenerative diseases include Alzheimer's disease and Pick's disease, which mainly affect the cerebral cortex; Parkinson's disease and Huntington's chorea, which mainly affect the basal ganglia; spinal cord-cerebellum degenerative disease, which mainly affects the cerebellum; and amyotrophic lateral sclerosis, which mainly affects the spinal cord. Neurodegenerative disease is rarely defined, even in textbooks. A possible definition for neurodegenerative disease may be as follows: a progressive disease which involves disorders of a certain system (such as the pyramidal tract system, funiculus dorsalis system, or spinal cord-cerebellum system) alone or in combination so as to manifest clinical symptoms which progress slowly and gradually, and for which the real cause cannot be determined (Ichiro KANAZAWA: Sai-shin Naikagaku Taikei, 68: p. 3, Nakayama Shoten (1997)).
Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease characterized by a selective disorder of motor neurons in the cerebral cortex, brain stem, and spinal cord, and the primary symptoms of ALS include progressive amyotrophia and hyper-reflex of deep tendon. Recently, there have been reported several cases, one after another, of spot mutations of Cu/Zn superoxide dismutase (SOD), which is a causal gene with respect to familial amyotrophic lateral sclerosis (FALS) and sporadic amyotrophic lateral sclerosis (SALS), and these reports have received much attention (Deng, H. et al.: Science, 261: 1047–1051, 1993; Rosen DR. et al.: Nature, 363: 59–62, 1993: Jones, CT. et al.: Lancet, 342: 1050–1061, 1993).
In efforts toward curing ALS, neuroprotective agents (anti-oxidants or anti-stimulants), neuroregeneratives and neurotrophic factors have been used, but only very weak effects have been observed. Specifically, the actions of ciliary neurotrophic factor (CNTF), insulin growth factor-1 (IGF-1), brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) against motor neuron injury have been reported, but the effects of these actions have remained weak and unsatisfying.